During the week of October 15, three persons died after
presenting to the Achuapa Health Center in Leon state (1995
population: 330,168), Nicaragua, with an acute febrile illness.
During the next 2 weeks, at least 400 persons were evaluated at
clinics in Achuapa (1995 population: 12,741) and nearby El Sauce
(1995 population: 24,289) for acute illnesses characterized by
fever, chills, headache, and musculoskeletal pain. As of November
7, approximately 150 of these patients and 150 persons from nearby
areas had been hospitalized in the regional medical center in Leon
because of more severe manifestations, including intense abdominal
pain, hypotension, and/or respiratory distress. At least 13 of the
patients have died from respiratory distress and pulmonary
hemorrhage. This report summarizes the preliminary findings of the
ongoing investigation of this outbreak by the Nicaraguan Ministry
of Health, the Pan American Health Organization, and CDC.

Dengue and dengue hemorrhagic fever were initially suspected
as the cause of the outbreak but were ruled out in Nicaragua and at
CDC by serologic tests and polymerase chain reaction assays of
serum specimens. Additional serologic tests found no significant
reactions to other arthropodborne and zoonotic pathogens, including
New World arenaviruses, lymphocytic choriomeningitis virus,
hantaviruses, other Bunyaviridae, Filoviridae, Flaviviridae,
Rhabdoviridae, Togaviridae, spotted-fever-group and typhus-group
rickettsia, Ehrlichia chaffeensis, and Coxiella burnetii.

Preliminary histopathologic examination at CDC of multiple
tissues from four decedents indicates features consistent with
leptospirosis. Specifically, silver impregnation staining of
autopsy specimens from two patients identified organisms with
typical leptospiral morphology in kidney and liver tissue; in a
third patient, leptospiral morphology was less typical. These
findings were confirmed by immunohistochemical staining using
rabbit polyclonal reference antiserum reactive with 16 different
leptospiral strains. Leptospiral antigens were seen as intact
leptospira, thread-like filaments, and granular forms in liver and
kidney tissue from three patients. Immunohistochemical tests of
these tissues with polyclonal antibodies were negative for dengue
virus, yellow fever virus, hantaviruses, arenaviruses and Ebola
virus.

Editorial Note

Editorial Note: The preliminary findings of this investigation
indicate that leptospirosis was the most likely cause of fatal
pulmonary hemorrhage in four hospitalized patients in Nicaragua.
Additional studies are under way to confirm the role of leptospiral
infection in the outbreak of acute febrile illness, establish
animal reservoirs of infection, and identify potentially modifiable
risk factors for disease. The investigation has thus far ruled out
the potential role of dengue virus and other arthropodborne and
rodentborne pathogens; in Central and South America, mosquitoborne
dengue is a leading cause of febrile illness, and the increasing
circulation of multiple dengue serotypes, including dengue type 3,
has been associated with an increase in reported hemorrhagic
manifestations of dengue (1,2).

Leptospirosis is a zoonotic disease of worldwide distribution,
involving many wild and domestic animals (3). Human infection may
result from indirect or direct exposure to infected urine, often
through contaminated water or soil. The investigation in Nicaragua
is examining the possibility that infection in humans resulted from
exposure to water and soil contaminated by animal urine following
recent heavy rainfall and flooding in that region.

The spectrum of leptospiral disease is broad and may include
fever, headache, chills, myalgia, abdominal pain, and conjunctival
suffusion; more severe manifestations include renal failure,
jaundice, meningitis, hypotension, hemorrhage, and/or hemorrhagic
pneumonitis (4). Severe pulmonary symptoms and pulmonary hemorrhage
have not been characteristic of leptospirosis in the Western
Hemisphere but have been associated with large outbreaks in Korea
and China (5,6). Clinical features of leptospirosis are similar to
many other febrile illnesses; in the tropics, the differential
diagnosis of such illnesses also may include dengue and malaria.
Leptospirosis is diagnosed by isolation of leptospires from blood
or cerebrospinal fluid during the acute illness and from urine
greater than or equal to 10 days after the onset of symptoms or by
documenting rising titers in serologic tests, such as the
microagglutination test.

Penicillin is the antibiotic of choice for leptospirosis, and
treatment should be initiated early in the course of illness (7).
Alternatives are amoxicillin, ampicillin, doxycycline, and
tetracycline. Supportive therapy is essential for managing
dehydration, hypotension, hemorrhage, renal failure, and pulmonary
involvement. For adults with short-term, high-risk exposure to
leptospirosis, doxycycline provides effective prophylaxis when
administered weekly in a single oral dose of 200 mg (8). Public
health measures include controlling rodents, preventing contact
with animal urine, wearing protective clothing (e.g.,
water-resistant boots) when exposure is likely, and avoiding
swimming or wading in potentially contaminated water (i.e., with
urine of infected animals).

Additional information is available from the CDC Fax
Information Service, telephone (404) 332-4565; enter document
number 221013# at the prompt.

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